The long-term objective of this work is to determine the role of leukocytes in human lung disease. The studies may lead to therapies to modify the human immune response. Integrins are a family of heterodimeric cell surface adhesion proteins that mediate attachment of cells to extracellular matrix proteins and vascular endothelial cells. The adhesion molecule integrin alpha 4 beta 7 is present on human lymphocytes and eosinophils. Integrin alpha 4 beta 7 mediates cell adhesion to mucosal addressin, a protein found on endothelial cells in mucosal tissues. Integrin alpha 4 beta 7 and mucosal addressin interact to direct leukocyte traffic into mucosal tissues. The aims of my work are to determine the amino acid residues of the cytoplasmic domain of the beta 7 integrin subunit that are involved in signal transduction by the integrin alpha 4 beta 7 and thereby play a role in regulation of leukocyte adhesion. The beta 7 subunit cDNA will be mutated to alter the structure and amino acid sequence of the cytoplasmic domain. The mutated beta 7 subunits will be expressed in cultured cell lines. In vitro assays will determine the effects of the cytoplasmic domain mutations on cell adhesion and signal transduction by integrin alpha 4 beta 7. Other experiments wil anaylze the function of alpha 4 beta 7 on human T cells.